BIOAVAILABILITY
Pharmacokinetics is the study of the fate of pharmaceuticals from the time they are ingested until they are eliminated from the body. The sequence of events for an oral composition includes absorption through the various mucosal surfaces, distribution via the blood stream to various tissues, biotransformation in the liver and other tissues, action at the target site, and elimination of drug or metabolites in urine or bile.
Bioavailability of a drug (pharmaceutical composition) following oral dosing is a critical pharmacokinetic determinant which can be approximated by the following formula: EQU F.sub.oral =F.sub.ABS .times.F.sub.G .times.F.sub.H
F.sub.oral is oral bioavailability fraction, which is the fraction of the oral dose that reaches the circulation in an active, unchanged form. F.sub.oral is less than 100% of the active ingredient in the oral dose for three reasons: drug is not absorbed through the GI tract and is eliminated in the feces; drug is biotransformed by the cells of the intestine (to an inactive metabolite); or drug is eliminated by the cells of the liver, either by biotransformation and/or by transport into the bile. Thus, oral bioavailability is the product of the fraction of the oral dose that is absorbed (F.sub.ABS), the fraction of the absorbed dose that successfully reaches the blood side of the gastrointestinal tract (F.sub.G), and the fraction of the drug in the GI blood supply that reaches the heart side of the liver (F.sub.H). Previous drug formulations have attempted to increase drug efficacy by increasing drug absorption. For example, methods have been used to increase drug absorption using liposomes as carriers and designing more lipophilic drugs. These methods can increase drug absorption; however, they fail to address other ways of increasing drug bioavailability.